Aedes aegypti sensu latu (s.l.) is the primary vector to humans of yellow fever virus (YFV) and the four serotypes of dengue virus (DENV1-4). Without a licensed vaccine for DENV, and despite the existence of a safe, effective YFV vaccine, control of these diseases still primarily relies on vector control. Our long term goal is to increase knowledge of local population dynamics to generate more focused, appropriate, and hopefully sustainable control strategies. There are two recognized subspecies of Ae. aegypti: the presumed ancestral form Ae. aegypti formosus (Aaf), a sylvan mosquito inhabiting forest habitats in sub-Saharan Africa;and Ae. aegypti aegypti (Aaa), found circumglobally in tropical and subtropical regions in close association with humans. We have been studying gene flow, vector competence and the distribution of Aaa and Aaf in Senegal. We present data that show a northwest-southeast cline in the abundance of the two subspecies. Northwest collections consist of only Aaa while collections in the southeast are all Aaf. The two subspecies were sympatric in six tall grass savanna and scrub sites in central Senegal. Consistent with the literature, competence for DENV2 is correlated with the distribution of the subspecies. Northwestern Aaa collections have a high disseminated infection rate (DIR) while southeast Aaf collections have a low DIR associated with a midgut escape barrier for DENV2. Curiously, our data and a recent publication suggest continuous gene flow across all geographic locations and subspecies in Senegal. This presents a paradox: How can the distribution of vector competence and subspecies be regional when gene flow is continuous? We present exciting data from a QTL mapping experiment gone wrong that demonstrate reduced recombination in Aaa/Aaf hybrids, consistent with an hypothesis that chromosomal inversions exist between the two subspecies. Inversions would allow for gene flow between subspecies while preserving associations in subspecies between morphological markers and vector competence. The possibility of inversions in Ae. aegypti s.l. has been discussed but never proven due to an inability to accurately resolve their polytene chromosomes. Our specific aims are to generate an intensive linkage map of Aaf to define presumptive inversions. Markers arising from this map will be used to define the geographic distribution of inversions in Senegal. We then propose to map Aaf QTL that condition susceptibility to DENV2 and YFV. We also plan to visit 50 additional sites in Senegal not covered in our initial survey to provide a more thorough coverage of vector competence and the prevalence of the subspecies. PUBLIC HEALTH RELEVANCE Reduction of yellow fever and dengue fever in humans is dependent on control of the mosquito Aedes aegypti. Genetic studies that offer insight into vector competence (i.e., the ability to carry and transmit virus) of this species group can more effectively target competent populations. Data suggest gene flow is rapid among geographically distinct populations of Aedes aegypti in Senegal, West Africa. But vector competence and the proportions of the Ae. aegypti aegypti and Ae. aegypti formosus subspecies differ among these same populations. Chromosomal inversions would allow gene flow between subspecies in this region while retaining subspecific morphological characteristics and vector competence. We propose to map the distribution and competence of Aedes aegypti in Senegal, identify the presumptive inversions, and use the genetic markers identified in association with these inversions to map the occurrence of these inversions in Senegal.